The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

A follow‐up study of electromagnetic interference of cellular phones on electronic medical equipment in the emergency department

Objective: Considering the growing use of cellular phones and the fast appearance of new phone models, the electromagnetic interference of currently popular cellular phones on electronic medical equipment was tested. Methods: Three Personal Communication System cellular phones were put at different distances from multiple electronic medical devices, the interference effect was observed and the electromagnetic field strength measured with a spectrum analyser. Results: Only two small pieces of equipment, the CO₂ airway adapter and the haemoglucostix meter were affected and then only when the phone was in very close proximity. Conclusion: Compared to the results of our study in 1997 testing Global System for Mobile Communication phones, the Personal Communication System phones generated less electromagnetic interference. However a much larger scaled study and an accurate international electromagnetic interference standard are recommended before any change in the current restrictive hospital policy on mobile phone usage could be recommended.     

Liver and lung resection for colorectal metastasis

Aim: To examine the survival benefit of liver and lung resection for colorectal metastasis and the potential prognostic factors that affect patient survival. Methods: All patients who had resection of lung or liver metastasis for colorectal metastasis in Queen Elizabeth Hospital, Hong Kong from 1995 to 2004 were retrospectively reviewed. The overall and disease‐free survival was analysed, in particularly between liver and lung metastasis. All factors that may have affected the survival were entered into Cox's proportional hazards regression model to identify significant variables associated with survival. Results: At 5 years, the overall survival of patients who had resection of lung and liver metastasis was 44% and 38%, respectively; the disease‐free survival was 26% and 24%, respectively. Overall and disease‐free survival of patients with resection of lung metastasis was comparable to those with resection of liver metastasis. The differentiations of primary tumour and time to metastasis were shown to be significant prognostic factors influencing overall survival. Those patients with systemic chemotherapy after resection of colorectal metastasis demonstrated a significantly higher probability of overall survival. Conclusion: Resection of lung and liver metastases from colorectal origin was safe and both procedures improved survival. The use of chemotherapy after resection of metastasis significantly improved the overall survival.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Manifestations and treatment of 793 cases of decompression sickness in a compressed air tunneling project in Hong Kong

In the largest compressed air tunneling contract for the construction of the Island Line of the Mass Transit Railway system in Hong Kong, 154,390 man-decompressions occurred, of which 142,140 were after exposures to 1 bar (1.97 ATA, 14.7 psig) or above. The maximum working pressure (MWP) was 3.30 bar (4.26 ATA, 47.9 psig). There were 792 cases of type I and 1 case of type II decompression sickness. The manifestations of the cases were generally similar to those reported elsewhere. Oxygen treatment was given to 9 cases and all were successfully treated with no recurrence of symptoms. Minimum effective pressure treatment on 783 type I cases was successful, with 9.6% requiring two or more recompressions. The pressure required to relieve symptoms was more closely related to the interval between completion of decompression after work and commencement of treatment than to the delay between onset of symptoms and treatment. For every 1-h interval or every 1-h delay, an additional pressure of 0.04 bar (0.04 ATA, 0.58 psi) above MWP was required for pain relief. Step-wise multiple regression analysis showed that the four predictors for pressure of relief and the highest pressure used in recompression, respectively, were, in order of descending importance, maximum working pressure, interval before treatment, bends sequence (the nth attack of bends experienced in the present contract, i.e., the sum of previous attacks and the present attack), and duration of exposure.     

Cell transplantation to improve ventricular function in the failing heart

Current therapies for congestive heart failure are limited in efficacy or in applicability. Cardiac cell transplantation offers a novel therapeutic approach to improve heart function. Although significant progress has been made over the past decade in the development of cell transplantation, only recently have investigators studied the changes in ventricular function following cell transplantation. This review article describes the latest research developments, evaluates recent studies of ventricular function after cell transplantation, and discusses the future directions of cell transplantation as a new therapy to ‘repair broken hearts’.     

Longitudinal study of cyclosporine and lipids in patients undergoing bone marrow transplantation

The metabolic effects of intravenous cyclosporine on lipids and lipoproteins were studied in 29 allogeneic bone marrow recipients compared with 13 autologous bone marrow patients not requiring cyclosporine therapy. Patients were monitored continuously from 5 days prior to 27 days following transplantation; cyclosporine treatment was initiated 4 days before transplantation. Fasting lipid and lipoprotein levels were measured in serial blood samples throughout the study period. Nutritional supplementation, conditioning regimens and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline between the patient groups. Cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels remained unchanged in autologous patients. As compared with baseline values, plasma total cholesterol increased by an average of 26 percent in allogeneic transplantation patients receiving cyclosporine. Similarly, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol was fourfold greater in those patients treated with cyclosporine compared to the autologous group. We conclude that cyclosporine appears to elevate cholesterol levels. Neither acute graft vs host disease nor changes in hepatic function could explain the differences in plasma cholesterol levels between groups.